Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia
Bruno Paiva, María-Belen Vidriales, Amparo Sempere, Fabián Tarín, Enrique Colado, Celina Benavente, María-Teresa Cedena, Joaquín Sánchez, Teresa Caballero-Velazquez, Lourdes Cordón, Juan-Jose Garces, Catia Simoes, David Martínez-Cuadrón, Teresa Bernal, Carmen Botella, Sofia Grille, Josefina Serrano, Carlos Rodríguez-Medina, Lorenzo Algarra, Juan-Manuel Alonso-Domínguez, María-Luz Amigo, Manuel Barrios, Raimundo García-Boyero, Mercedes Colorado, Jaime Pérez-Oteyza, Manuel Pérez-Encinas, Lisette Costilla-Barriga, María-José Sayas, Olga Pérez, Marcos González-Díaz, José A Pérez-Simón, Joaquín Martínez-López, Claudia Sossa, Alberto Orfao, Jesús F San Miguel, Miguel-Ángel Sanz, Pau Montesinos, PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group
The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry.
We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors.
Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.